Eugene Marcantonio, MD, PhD

Research in my lab is focused on the regulation and intracellular signaling of integrin receptors. Integrins are receptors for extracellular matrix proteins and their intracellular domains are specialized to provide a tensile link between the cell's exterior and its internal actin-based cytoskeleton, which is critical for cell migrations during embryonic development. In addition, integrins also generate intracellular signals required for T cell development, anchorage-dependent cell cycle progression, and other biological processes.

Our major aim is to identify the most proximal events in integrin-mediated signal transduction using a variety of approaches. Our systems include: expression of mutant integrins in fibroblasts; transgenic mice, T cell activation, and fluorescent microscopy of live cells using Green fluorescent protein probes. Through our recent work, it has become clear that there are at least two signal transduction pathways downstream of integrins. One leads to organization of the actin cytoskeleton into discrete subcellular structures, through the action of the tyrosine kinase pp125FAK. Another activates the p21ras pathway, through the adapter protein Shc. We are using single-subunit integrin chimeras to precisely identify the domains and proteins involved in the interaction with the actin cytoskeleton. In addition, we are identifying other transmembrane proteins which are critical for linking integrins to the p21ras pathway via Shc. These experiments are linked in vivo by our transgenic mice, which express integrin dominant negatives in the thymus. These constructs interfere with normal T cell development.

Another focus of the lab is the role of integrins in the migration and proliferation of vascular smooth muscle cells in atherosclerosis. We have cloned the major human integrin receptor integrin of vascular smooth muscle cells, and are investigating the migration and growth of these cells in atherosclerosis.

Selected Publications:

• Briesewitz, R., Kern, A., and Marcantonio, E.E. Assembly and function of integrin receptors is dependent on opposing alpha- and beta-cytoplasmic domains. Mol. Biol. Cell 6: 997-1010 (1995).

• Wary, K.K., Mainero, F., Isakoff, S.J., Marcantonio, E.E., and Giancotti, F.G. The adaptor protein Shc couples a class of integrins to the control of cell cycle progression. Cell 87: 733-743 (1996).

• Assoian, R.K., and Marcantonio, E.E. The extracellular matrix as a cell cycle control element in atherosclerosis and restenosis. J. Clin. Invest. 98: 2436-2439 (1996).

• Marcantonio, E.E. and David, F.S. Integrin receptor signaling: The propagation of a helix model. Matrix Biol. 16: 179-184 (1997).